Small Doses Probed in Gulf Illness

WASHINGTON —  Researchers studying the mysterious illnesses of Persian Gulf War veterans are now searching for answers that could sweep aside medical dogma and raise disturbing possibilities about the dangers of a variety of substances used in everyday life, as well as in war.

With all studies to date failing to find a common cause for the undiagnosed illnesses of thousands of veterans, an urgent priority of the multimillion-dollar research effort is to determine: Could a small number of chemical exposures at levels so low that they produce no immediate symptoms cause serious health effects years later?

Medical science, based on decades of work, has held that this is unlikely. But now, alerted by what may have happened to troops in the toxin-laden Gulf War theater, scientists are taking seriously the notion that there may be risks in such barely detectable exposures.

If their findings are positive, researchers and public health authorities could face troubling uncertainties about the effects of all sorts of substances--uncertainties such as those that have haunted modern life in periodic controversies over food dyes, pesticides and even electromagnetic fields, officials say.

“This is the most significant scientific question we’re trying to answer,” said Dr. Stephen C. Joseph, the Pentagon’s top physician.

Timothy R. Gerrity, who oversees the design of new research projects for the Department of Veterans Affairs, said the research “could open up a Pandora’s box” of questions with wide public policy implications.

Prompting the research has been the unexplained symptoms of thousands of GIs who went to the Persian Gulf to fight Iraq in 1991. Although most of these 697,000 U.S. troops left for the Middle East in top condition, after they returned, thousands began reporting chronic fatigue, nausea, insomnia, rashes, memory and thinking problems, indigestion and aching joints.

Researchers have been exploring a variety of possible causes for their symptoms. But a class of chemicals called organophosphates has been getting particular attention since June, when the Pentagon disclosed that thousands of soldiers may have been exposed to chemical weapons at the war’s end.

The possible exposure took place in March 1991, when U.S. troops in a postwar mop-up operation blew up an Iraqi munitions storage facility at Khamisiyah in southern Iraq.

Until learning of that incident, government researchers had found little reason to believe chemical-war agents might have played a role in the ailments.

These gases--known by such names as sarin and soman--set off violent reactions as they increase the activity of substances that send nerve impulses across synapses. In dangerous doses, they bring on wheezing, vomiting, convulsions and a quick death.

Researchers had largely ruled them out in the veterans’ illnesses because decades of medical studies showed that these chemical weapons either produce acute and immediate symptoms or they produce no health problems at all.

But experts now acknowledge that there has been a gap in medical research. For reasons that are perhaps understandable, studies of these gases had always focused on people who showed symptoms soon after their exposure. They didn’t track what happened to people who were near an exposure but registered no signs that they had gotten a dose, because these people were thought unlikely to ever have a health problem.

The research on these chemicals “has been voluminous--but it hasn’t been complete,” said Joseph, the assistant secretary of Defense for health affairs.

The government is gearing up an initial round of research that will focus on the nerve gases and certain pesticides that are related, although not identical, to members of the organophosphate class of chemicals.

If that research finds links between exposures and illnesses, it will have implications for all sorts of substances that aren’t related to organophosphates because it would suggest that some biological mechanisms can be harmed by even a few mild chemical exposures.

Modern medicine has chronicled in great detail how some substances--such as tobacco, asbestos and lead--can produce long-term health damage through low-level but repeated exposures.

This case, however, involves soldiers who were apparently exposed only once or a few times at most to these chemical weapons, although they may have had multiple exposures to the insect repellents and anti-nerve-gas medicine that some investigators believe may have played a big role in the complaints.

If the research turns up causes for illnesses, it will suggest that further studies are needed on all sorts of substances that have been thought safe for everyday use. Researchers say it is speculative to try to identify the chemicals that would come under suspicion.

But such conclusions would raise obvious questions about related pesticides--even in low-dose forms--such as fly strips, solvents and related chemicals. Investigators might also be asking questions about medicines, dyes, even such things as the electromagnetic fields generated by power lines, some researchers say.

The question then would be “much broader than a military or national security issue,” said Joseph, who formerly headed the New York City Health Department. In this eventuality, “you’re back into a Red Dye No. 2, microwave-transmissions kind of setting, which could make for a very volatile scientific-policy issue, and legal-policy issue.”

Joseph and the other experts stress that researchers are a long way from reaching such conclusions.

To date, the government has set aside about $15 million for research on such low-level chemical exposures.

On one front, investigators for the Pentagon and other agencies are trying to piece together what happened at Khamisiyah. That undertaking faces immense complications.

Authorities still aren’t clear on how much gas may have been released or the location of all the troops who might have been exposed. As a result, most investigators expect that the basic facts will remain sketchy.

“The Khamisiyah studies may give some hints, but we’ll have a hard time coming up with a powerful statistical associations, just because of the limitations of the data,” said Thomas Louis, a biostatistician at the University of Minnesota who served on a panel of experts that last year looked at the issue.

On another track, researchers will examine how laboratory animals respond to low-level chemical warfare agents, such as sarin, and related organophosphate pesticides.

In addition, researchers are expected to examine groups of humans who have been exposed to organophosphates in various ways.

One group that is likely to be studied in detail are the Japanese commuters who were exposed to sarin gas in two 1995 attacks by the terrorist group Aum Supreme Truth. The attacks killed 11 people and injured 5,500 in Tokyo.

Another group expected to be examined are the agricultural workers who are routinely exposed to small amounts of pesticides used on crops.

Researchers acknowledge that even in the case of people who have had a well-known exposure to chemicals it will be tricky to determine the cause of health effects that show up years later.

“Once you get into the realm of things that have a long latency period, ascribing that outcome to something that happened 20 years ago along with a lot of other things becomes conceptually . . . very difficult,” Louis said.

Most researchers predict that the findings won’t be in for years. But they contend that the effort will find answers, despite the elusiveness of the subject, and the long-established orthodoxy suggesting that such effects simply weren’t possible.

“Scientific orthodoxy exists to be overturned,” Joseph said.